PROJECT ABSTRACT In response to community requests, a Navajo Birth Cohort will be developed to study the prenatal, perinatal, and early postnatal health effects of environmental exposures to uranium and associated mining wastes on Navajo mothers and their offspring through the following specific aims: Aim 1: Co-operatively design and conduct a prospective epidemiologic birth cohort study of pregnancy outcomes and child development in relation to uranium waste exposures among Navajo mother-infant pairs. 1. Solicit community, Navajo and federal agency input, to inform the final study design to ensure it is respectful of Navajo culture and includes appropriate measures to address community concerns 2. Enroll 1,650 pregnant women in early pregnancy (1st or early 2nd trimester, as feasible) and follow them throughout pregnancy and childbirth (assumes a pregnancy loss rate of 10%) 3. Establish a birth cohort of 1,500 offspring of these women who will be assessed and followed for birth, growth, and neurodevelopmental outcomes to 12 months of age (in the initial phase of follow-up) 4. Compare health endpoints (as finalized by the expanded Research Team) among mothers and their children who are more and less likely to be exposed to uranium and associated metals. Aim 2: Characterize the cohort with respect to mobility, exposures, co-exposures, demographic and cultural characteristics that may influence outcomes 1. Measure/estimate human exposures to uranium and other toxicants, and identify exposure pathways 2. Use geospatial statistics to identify exposure hot spots as surrogates for exposure 3. Collect information on potential modifiers of susceptibility, such as diet and psychosocial stress Aim 3: With guidance from our expanded Community Liaison Group (CLG) and collaboration with community health workers, provide extensive outreach on the study goals and results, on prenatal care, available clinical services, and mitigation of any exposure-induced health effects on Navajo. Aim 4: Work with Navajo agency partners to develop their environmental health capacity and to develop a sustainability plan for continued follow-up of the cohort. This work will be accomplished through a cooperative agreement with ATSDR/CDC and involve agency scientists as well as communities in development and implementation of the final design. The Research Team combines scientific expertise in epidemiology, toxicology, mathematics and modeling, and environmental assessment with participation of Navajo culture and language experts, traditional medicinemen, and Navajo Nation agencies as well as clinical care providers to ensure not only respectful design and implementation, but effective translation of the results to policy, health care, and effective outreach and education for communities.